Fibroblasts are the major cell type responsible for the synthesis of collagen, a fibrous protein essential for maintaining the integrity of the extracellular matrix found in the dermis of the skin and other connective tissues. The production of collagen is a finely regulated process, and its disturbance may lead to the development of tissue fibrosis. The formation of fibrous tissue is part of the normal beneficial process of healing after injury. However, in some circumstances there is an abnormal accumulation of fibrous material such that it interferes with the normal function of the affected tissue.
Central to the development of fibrotic conditions, whether spontaneous or induced, is stimulation of fibroblast activity. Many common debilitating diseases, such as liver cirrhosis and pulmonary fibrosis, involve the proliferation of fibrous tissue as do certain skin diseases such as scleroderma, keloids, and hypertrophic scars.
Excessive accumulation of collagen in the extracellular matrix, resulting from exuberant fibroblast proliferation and/or collagen production, is a major biochemical abnormality in the fibrosis of a number of tissues including the skin. Attempts to control the abnormal accumulation of collagen have focused on several inhibitors of the translational and posttranslational reactions in collagen biosynthesis, but their therapeutic value is limited by certain undesirable features, i.e., poor permeability across cell membrane, nonspecificity in action, or toxicity. There is, accordingly, a continuing need for new antifibrotic agents.